A major goal in the study of learning and memory is the identification of the molecular changes following learning which result in long-term memory formation. Recently, a body of evidence has accumulated implicating trophic factors as essential components of learning-related molecular signaling, however the underlying cellular mechanisms are poorly understood. The scope of this project is to investigate the roles of immediate intracellular transducers of trophic factor signaling, Grb2 and PLCgamma1, in hippocampus-dependent learning and memory, and to investigate whether they contribute to learning induced activation of a well-established molecular player in learning and memory, the extracellular signal-regulated kinase (ERK). My working hypothesis is that Grb2 and/or PLCgamma1 will be necessary for long-term hippocampus dependent memory. This effect may be mediated via ERK, which is a target for the signaling cascades downstream from both of these molecules. Based on the current literature and preliminary results, I propose a study with the following Specific Aims: Aim 1: To determine if Grb2 and/or PLCgamma1 mediated signaling contributes to ERK activation following NGF stimulation in vitro, and following behavioral training in vivo. Aim 2: To determine if Grb2 mediated signaling is involved in hippocampus dependent long-term memory formation. Aim 3: To determine if PLCgamma1 mediated signaling is involved in hippocampus dependent long-term memory formation.